Aldo-keto reductase

Machielsen, R., Uria, A.R., Kengen, S.W.M. and van der Oost, J. (2006) Production and characterization of a thermostable alcohol dehydrogenase that belongs to the aldo-keto reductase superfamily. Applied and Environmental Microbiology, 72 (1), 233-238. 

The peptide sequences obtained for codeinone reductase aligned well with the amino acid sequences for 6 -deoxychalcone synthase (chalcone reductase) from alfalfa, Glycerrhiza, and soybean. Knowledge of the relative positions of the peptides allowed for a quick RT-PCR based isolation of cDNAs encoding codeinone reductase from P. somniferum. The codeinone reductase isoforms are 53 % identical to chalcone reductase from soybean.25 By sequence comparison, both codeinone reductase and chalcone reductase belong to the aldo/keto reductase family, a group of structurally and functionally related NADPH-dependent oxidoreductases, and thereby possibly arise from primary metabolism. Six alleles encoding codeinone... 

FIGURE 5.1 Reduction of specific substrates for aldo/keto reductases. 

Molowa DT, Wrighton SA, Blanke RV, et al. 1986b. Characterization of a unique aldo-keto reductase responsible for the reduction of chlordecone in the liver of the gerbil and man. J Toxicol Environ Health 17 375-384. 

A further remarkable finding in the hydrolysis of aflatoxin B1 exo-8,9-epoxide is the relative instability of the dihydrodiol, which under basic conditions exists in equilibrium with an aflatoxin dialdehyde, more precisely a furofuran-ring-opened oxy anionic a-hydroxy dialdehyde (10.134, Fig. 10.30). The dihydrodiol is the predominant or exclusive species at pH < 7, whereas this is true for the dialdehyde at pH >9, the pK value of the equilibrium being 8.2 [204], The dialdehyde is known to form Schiff bases with primary amino groups leading to protein adducts. However, the slow rate of dialdehyde formation at physiological pH and its reduction by rat and human aldo-keto reductases cast doubts on the toxicological relevance of this pathway [206]. 

Reduction Carbonyl groups. The carbonyl group (-(C=0)-) is reduced through a reaction that is catalyzed by an aldo-keto reductase requiring NADH as a cofactor. A large number of aromatic and aliphatic ketones are reduced to the corresponding alcohols these reductions are frequently stereospecific. a,P-Unsaturated ketones are typically metabolized to saturated alcohols. 

Brozic, P, Turk, S., Lanisnik Rizner, T., Gobec, S. (2009) Discovery of new inhibitors of aldo-keto reductase 1C1 by structure-based virtual screening. Mol Cell Endocrinol 301,245-250. 

V. Aldo-Keto Reductase Family A Effects of Sequence on Drug Design... 

Pailhoux EA, Martinez A, Veyssiere GM, Jean CG. Androgen-dependent protein from mouse vas deferens cDNA cloning and protein homology with the aldo-keto reductase superfamily. J Biol Chem 1990 265 19932-19936. 

Wilson DK, Nakano T, Petrash JM, Quiocho FA. 1.7 A structure of FR-1, a fibroblast growth factor-induced member of the aldo-keto reductase family complexed with coenzyme and inhibitor. Biochemistry 1995 34 14323-14330. 

Hoog SS, Pawlowski JE, Alzari PM, Penning TM, Lewis M. Three-dimensional structure of rat liver -hydroxysteroid/dihydrodiol dehydrogenase a member of the aldo-keto reductase superfamily. Proc Natl Acad Sci USA 1994 91 2517-2521. 

Other alcohol dehydrogenases and aldo-keto reductases... 

The active sites of aldo-keto reductases contain an essential tyrosine (Tyr 48) with a low pfCa value. 

C Kinetic isotope effects (KIEs) of a xylose reductase-catalysed cinnamalde-hyde reduction have been determined by 13C NMR using competition reactions with reactants at natural 13C abundance. The primary KIEs indicated that the chemical reaction steps are only partly rate limiting during reduction of aromatic aldehydes and slow steps occur outside the catalytic sequence. The aldo-keto reductase-catalysed... 

Carbonyl Reductase Inhibition (Aldo-Keto-Reductase Family of Enzymes)... 

The enzyme giving (ft)-4-chIoro-3-hydroxybutanoate esters was isolated in crystalline form from S. salmonicolor and was characterized in some detail [111-113], It is a kind of aldehyde reductase with a molecular mass of about 37,000. The enzyme absolutely requires NADPH as a cofactor. Besides 4-haloacetoacetate esters, p-nitrobenzaldehyde and a variety of other aromatic and aliphatic aldehydes have been found to be reduced well by the enzyme (see Tables 4 and 5). The structural gene of the enzyme was cloned and the enzyme has shown to have similarity to the mammalian aldo-keto-reductase superfamily enzymes in primary protein structure [114], In S. salmonicolor, the enzyme comprised 2 6% of the total extractable proteins. Such a high content of the enzyme suggests that this may be one of the reasons why the yeast catalyzes conversion to the (R)-enantiomer predominantly. 

Aldo-keto reductase YPRl Ydr368w 34,622 6.88 Viable Soluble... 

Aldo-keto reductases (Fig. 7A) Ile-Pro-Lys-Ser-X5-Arg Exact match in Gre3p others have related sequences 63... 

K Nakamura, S Kondo, Y Kawai, N Nakajima, A Ohno. Amino acid sequence and characterization of aldo-keto reductase from baker s yeast. Biosci Biotechnol Biochem 61 375-377, 1997. 

JM Jez, TG Flynn, TM Penning. A new nomenclature for the aldo-keto reductase superfamily. Biochem Pharmacol 54 639-647, 1997. 

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